Lung Cancer Screening and Prevention: Beyond Conventional Strategies in a Rapidly Changing Global Milieu

Lung cancer remains the leading cause of cancer-related mortality worldwide despite advances in early detection and treatment. Furthermore, its epidemiology has undergone a profound transformation, necessitating a radical and comprehensive departure from traditional oncology frameworks. The historical paradigm, which focuses almost exclusively on tobacco smoking as the primary etiological driver, is increasingly inadequate to address the escalating global burden of lung cancer in never-smokers (LCINS). This epidemiologic shift is particularly evident in East Asian populations, where LCINS has transitioned from being a perceived outlier to becoming the dominant clinical phenotype, representing over 60% of all diagnosed cases in certain demographics especially in women. This comprehensive review integrates the exposome framework: a holistic methodology evaluating the cumulative and synergistic endogenous and environmental impact of air, water, and food pollutants across the human lifespan, with the practical and logistical implementation of precision screening. The addition of humanomics expands the concept of exposome to include societal structural inequalities. Rethinking lung cancer screening beyond a single imaging modality also requires a stronger focus on health equity. By synthesizing longitudinal data from the landmark TALENT study and integrating cutting-edge technologies such as artificial intelligence-driven risk prediction (Sybil) and advanced molecular triage using circulating tumor DNA, we advocate for a radical transition toward comprehensive computed tomography screening. This multisystem approach maximizes public health return on investment by simultaneously intercepting lung cancer, cardiovascular disease, and chronic respiratory illnesses at their earliest preclinical, asymptomatic, and most treatable stages.